This research program has been constructed with a primary aim of investigating various aspects of the immunology and immunopathology associated with the aging process. It has been well documented that aging is associated with varying degrees of immunologic abnormalities, some of which represent deficiencies in immune function, others representing aberrantly excessive immune reactivity, particularly to autologous or self-antigens. In addition, aging is accompanied by a variety of immunopathologic consequences, some of which are primary, others secondary in nature. This program project brings together several senior scientists from our two respective institutions who have special expertise in various aspects of immunology and immunopathology. Collectively, these studies are designed to address certain key questions concerning immunologic control mechanisms (Research Program I), the fastidiousness of B lymphocyte receptor diversity (Research Program II), and, lastly, the possible consequences of aberrant immunologic responses leading to certain autoimmune manifestations which may underlie at least some of the pathogenesis of age-related arteriovascular diseases (Research Program III). The knowledge forthcoming from this program should provide new insights, based on modern-day technical approaches performed in highly accomplished laboratories, to the basic mechanisms underlying immunologic deficiencies and other abnormalities associated with the aging process.